Artículos (Farmacología, Pediatría y Radiología)

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Optimising urinary catecholamine metabolite diagnostics for neuroblastoma
(Wiley, 2023-04-03) Matser, Yvette A.H.; Verly, Iedan R.N.; van der Ham, Maria; de Sain-van der Velden, Monique G.M.; Verhoeven-Duif, Nanda M.; Ash, Shifra; Cangemi, Giuliana; Barco, Sebastiano; Popovic, Maja Beck; van Kuilenburg, André B.P.; Tytgat, Godelieve A.M.; Márquez Vega, Catalina; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Villa Joep Foundation
Introduction: The analysis of urinary catecholamine metabolites is a cornerstone of neuroblastoma diagnostics. Currently, there is no consensus regarding the sampling method, and variable combinations of catecholamine metabolites are being used. We investigated if spot urine samples can be reliably used for analysis of a panel of catecholamine metabolites for the diagnosis of neuroblastoma. Methods: Twenty-four-hour urine or spot urine samples were collected from patients with and without neuroblastoma at diagnosis. Homovanillic acid (HVA), vanillylmandelic acid (VMA), dopamine, 3-methoxytyramine, norepinephrine, normetanephrine, epinephrine and metanephrine were measured by high-performance liquid chromatography coupled with fluorescence detection (HPLC-FD) and/or ultra-performance liquid chromatography coupled with electrospray tandem mass spectrometry (UPLC-MS/MS). Results: Catecholamine metabolite levels were measured in urine samples of 400 neuroblastoma patients (24-hour urine, n = 234; spot urine, n = 166) and 571 controls (all spot urine). Excretion levels of catecholamine metabolites and the diagnostic sensitivity for each metabolite were similar in 24-hour urine and spot urine samples (p > .08 and >.27 for all metabolites). The area under the receiver-operating-characteristic curve (AUC) of the panel containing all eight catecholamine metabolites was significantly higher compared to that of only HVA and VMA (AUC = 0.952 vs. 0.920, p = .02). No differences were observed in metabolite levels between the two analysis methods. Conclusion: Catecholamine metabolites in spot urine and 24-hour urine resulted in similar diagnostic sensitivities. The Catecholamine Working Group recommends the implementation of spot urine as standard of care. The panel of eight catecholamine metabolites has superior diagnostic accuracy over VMA and HVA.
Prevalencia, hábitos de consumo y complicaciones de los suplementos nutricionales proteicos en adolescentes
(Elsevier, 2023-09-15) Millán Jiménez, Antonio; Fernández Fontán, Isabel María; Sobrino Toro, Manuel; Fernández Torres, Bartolomé; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Universidad de Sevilla. Departamento de Cirugía
Introducción: El consumo de suplementos nutricionales y proteicos por adolescentes puede tener importantes repercusiones para su salud. Material y método: Estudio prospectivo observacional, basado en una encuesta, dirigido a los adolescentes de seis colegios, seleccionados aleatoriamente, de la ciudad de Sevilla. Nuestro objetivo principal es conocer el consumo real de suplementos alimentarios entre la población adolescente, cuantificando su contenido proteico. Resultados: Se obtuvieron 263 respuestas válidas, objetivando una prevalencia de consumo de 19,01% para todos los suplementos nutricionales, de ellos 56,0% tomaban suplementos de proteínas (10,64% del total), con una ingesta media de estas últimas de 0,26 ± 0,18 g/kg/día. El perfil del consumidor de cualquier tipo de suplementos se diferencia del de los que no los utilizan en la edad, el uso de medicación habitual y realizar dieta para perder peso o hiperproteica. Al comparar los adolescentes que ingerían productos proteicos con los no proteicos, la única variación significativa estuvo en el control del consumo. Aunque la mayoría no tiene control externo, en 25,92% de los que tomaban proteínas el seguimiento lo hacía un profesional, vs. 7,38% de los que ingerían suplementos no proteicos. De los consumidores de productos proteicos, 85,18% consiguió el objetivo buscado y 18,51% refirió algún efecto negativo. Conclusiones: La prevalencia de consumo de suplementos proteicos entre los adolescentes de nuestro medio es del 10,64%, en cantidades que suponen un 25% de las proteínas que deben ingerir diariamente. El perfil de consumidor de suplementos proteicos es muy similar al de aquel que toma productos no proteicos.
Psychometric evaluation of the Spanish version of the Pediatric Quality of Life Eosinophilic Esophagitis Questionnaire (Peds QL-EoE Module ™)
(BioMed Central, 2023-12-13) García-Martínez de Bartolomé, Ruth; Barrio Torres, Josefa; Cilleruelo Pascual, María Luz; Rodríguez Soler, Juan José; Gil de Miguel, Ángel; Sebastián Viana, Tomás; Millán Jiménez, Antonio; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Background: The Paediatric Eosinophilic Oesophagitis Module (PedsQL-EoE) was developed in English as a valid and reliable questionnaire to assess health-related quality of life (HRQoL) in children with EoE. The aim of this study was to evaluate the validity and reliability of the PedsQL-EoE that was previously adapted to Spanish by our group. Methods: This cross-sectional multicentre study was conducted in 36 paediatric gastroenterology units. Groups with and without dietary restrictions were studied separately. The PedsQL-EoE consists of 33 items divided into seven factors. Age-specific versions of the PedsQL-EoE were sent by e-mail to children and parents. Statistical analysis was used to study the questionnaire structure by means of exploratory factor analysis and interitem correlations. Confirmatory factor analysis (CFA) was applied to verify the proposed model as well as its psychometric properties through SMSR (standardized root mean square), outer loadings and R-square. To study construct validity and reliability, Cronbach´s alpha coefficient, convergent validity (AVE), discriminant validity (HTMT) and intraclass correlation coefficients (ICC) were used. Results: A total of 341 children and 394 parents participated with 307 matched answers. The median age was 12 years, and 75% were male. The questionnaire structure explained 68% and 66% of the total variance for parents and children, respectively. Five items showed negative correlations and were removed from the questionnaire. CFA applied to the new model supported the following construct: SMRS was less than 0.08, outer loadings measured above 0.5, and R2 explained more than 89% of the total variance. Once the modifications were performed, good internal consistency was demonstrated, with Cronbach’s alpha values > 0.7, AVE values > 0.5 and HTMT < 0.9 with good child/parent agreement (ICC = 0.80). The most robust model of the PedsQL-EoE module was formed by seven factors: Symptoms I (6 items), Symptoms II (4 items), Treatment (4 items), Worries (3 items), Communication (5 items), Food and Eating (3 items) and Food Feelings (3 items). Conclusions: The final PedsQL-EoE Module version, after the removal of five items, is a valid and reliable tool to be used in children with EoE. The Spanish validated version appears to be a useful instrument for measuring the impact of EoE on Spanish children´s quality of life.
Characterization of Rugulopteryx okamurae algae: A source of bioactive peptides, omega-3 fatty acids, and volatile compounds
(Elsevier, 2025-05-01) Rivero Pino, Fernando; González de la Rosa, Teresa; Torrecillas López, María; Barrera Chamorro, Luna; Río-Vázquez, José Luis del; Márquez Parada, Elvira; Fernández Prior, África; Garcáa-Vaquero, Marco; García Gómez, José Carlos; Montserrat de la Paz, Sergio; Claro Cala, Carmen María; Universidad de Sevilla. Departamento de Zoología; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
This study provides a detailed characterization of the invasive algae Rugulopteryx okamurae, highlighting its nutritional composition, mineral content, and potential bioactive compounds. This biomass contains 14.18 % protein, 21.29 % lipids (with a high omega-3 content), fibre (31.32 %), and significant amounts of minerals like calcium, sodium, potassium, sulphur, and iron. Phenolic compounds (0.74 %) and volatile compounds, such as retinol, were also identified. Peptidome analysis revealed 626 unique peptides, with 21 low molecular weight peptides showing potential activity against angiotensin converting enzyme and dipeptidyl peptidase IV when assessed using in silico tools and using molecular docking. Additionally, the antioxidant capacity of the alga was demonstrated with a significant free radical inhibition (EC50: 2.09 mg/mL). Overall, this study provides initial evidence on the nutritional potential of R. okamurae, which may have potential for future applications in food and biotechnology fields.
Recent Evidence-Based Clinical Guide for the Use of Dinutuximab Beta in Pediatric Patients with Neuroblastoma
(Springer Adis, 2022-12-12) Balaguer, Julia; García Hidalgo, Laura; Hladun, Raquel; Márquez Vega, Catalina; Pérez Alonso, Vanesa; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
The anti-GD2 antibody dinutuximab beta (Qarziba®) has been added to the present standard of care for patients with high-risk neuroblastoma in Europe based on the positive results obtained in different studies. In both the first-line and relapsed/refractory settings, treatment with dinutuximab beta attains objective clinical responses in children with high-risk neuroblastoma. Its incorporation has changed the outcome for these patients and optimized management should be guaranteed to minimize possible adverse effects. Most prevalent adverse events include pain, allergic reactions, fever and capillary leak syndrome. There are still no evidence-based clinical guidelines that include the latest published evidence to optimize its use, as it depends on the experience gained in each referral center. Topics such as the mode of preparation and administration, the concomitant use of interleukin-2, the recommended pediatric age and dose for its use, or the adequate management of possible toxicities are important aspects to review. The objective of this article was to update the clinical guide to management with dinutuximab beta of children with neuroblastoma based on the most recent published evidence and our own experience in clinical practice.
Response-adapted omission of radiotherapy in children and adolescents with early-stage classical Hodgkin lymphoma and an adequate response to vincristine, etoposide, prednisone, and doxorubicin (EuroNet-PHL-C1): a titration study
(Elsevier, 2023-03) Mauz-Körholz, Christine; Landman Parker, Judith; Fernández-Teijeiro, Ana; Attarbaschi, Andishe; Balwierz, Walentyna; Bartelt, Jörg Martin; Kluge, Regine; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Background: Children and adolescents with early-stage classical Hodgkin lymphoma have a 5-year event-free survival of 90% or more with vincristine, etoposide, prednisone, and doxorubicin (OEPA) plus radiotherapy, but late complications of treatment affect survival and quality of life. We investigated whether radiotherapy can be omitted in patients with adequate morphological and metabolic responses to OEPA. Methods: The EuroNet-PHL-C1 trial was designed as a titration study and recruited patients at 186 hospital sites across 16 European countries. Children and adolescents with newly diagnosed stage IA, IB, and IIA classical Hodgkin lymphoma younger than 18 years of age were assigned to treatment group 1 to be treated with two cycles of OEPA (vincristine 1·5 mg/m2 intravenously, capped at 2 mg, on days 1, 8, and 15; etoposide 125 mg/m2 intravenously, on days 1–5; prednisone 60 mg/m2 orally on days 1–15; and doxorubicin 40 mg/m2 intravenously on days 1 and 15). If no adequate response (a partial morphological remission or greater and PET negativity) had been achieved after two cycles of OEPA, involved-field radiotherapy was administered at a total dose of 19·8 Gy (usually in 11 fractions of 1·8 Gy per day). The primary endpoint was event-free survival. The primary objective was maintaining a 5-year event-free survival rate of 90% in patients with an adequate response to OEPA without radiotherapy. We performed intention-to-treat and per-protocol analyses. The trial was registered at ClinicalTrials.gov (NCT00433459) and with EUDRACT, (2006–000995-33) and is completed. Findings: Between Jan 31, 2007, and Jan 30, 2013, 2131 patients were registered and 2102 patients were enrolled onto EuroNet-PHL-C1. Of these 2102 patients, 738 with early-stage disease were allocated to treatment group 1. Median follow-up was 63·3 months (IQR 60·1–69·8). We report on 714 patients assigned to and treated on treatment group 1; the intention-to-treat population comprised 713 patients with 323 (45%) male and 390 (55%) female patients. In 440 of 713 patients in the intention-to-treat group who had an adequate response and did not receive radiotherapy, 5-year event-free survival was 86·5% (95% CI 83·3–89·8), which was less than the 90% target rate. In 273 patients with an inadequate response who received radiotherapy, 5-year event-free survival was 88·6% (95% CI 84·8–92·5), for which the 95% CI included the 90% target rate. The most common grade 3–4 adverse events were neutropenia (in 597 [88%] of 680 patients) and leukopenia (437 [61%] of 712). There were no treatment-related deaths. Interpretation: On the basis of all the evidence, radiotherapy could be omitted in patients with early-stage classical Hodgkin lymphoma and an adequate response to OEPA, but patients with risk factors might need more intensive treatment.
Long-term efficacy and safety of vestronidase alfa enzyme replacement therapy in pediatric subjects < 5 years with mucopolysaccharidosis VII
(Elsevier, 2023-03-09) Lau, Heather A.; Viskochil, David; Tanpaiboon, Pranoot; González-Meneses López, Antonio; Martins, Esmeralda; Taylor, Julie; Malkus, Betsy; Zhang, Lin; Jurecka, Agnieszka; Marsden, Deborah; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Mucopolysaccharidosis (MPS) VII is an ultra-rare, autosomal-recessive, metabolic disease caused by a deficiency of β-glucuronidase, a lysosomal enzyme that hydrolyzes glycosaminoglycans (GAGs), including dermatan sulfate (DS), chondroitin sulfate, and heparan sulfate (HS). β-glucuronidase deficiency leads to progressive accumulation of undegraded GAGs in lysosomes of affected tissues, which may cause hydrops fetalis, short stature, hepatosplenomegaly, and cognitive impairment. An open-label, multicenter, phase II study was conducted in 8 pediatric subjects <5 years of age with MPS VII. Subjects received the recombinant human β-glucuronidase vestronidase alfa 4 mg/kg by intravenous infusion every other week for 48 weeks (treatment period). Those who completed the 48-week treatment were offered to continue treatment with vestronidase alfa 4 mg/kg for up to 240 weeks or until withdrawal of consent, discontinuation, or study termination (continuation period). The level of GAG excreted in urine (uGAG) above normal has been shown to correlate with disease severity and clinical outcomes in MPS diseases. Therefore, the primary efficacy endpoint of this study was to determine the mean percentage change in uGAG DS excretion from baseline to week 48. Statistically significant reductions in uGAG DS from baseline were observed at each visit (p < 0.0001), with a least square mean (standard error) percentage change of −60% (6.6) at week 4 (first post-baseline assessment) and −61% (6.41) at week 48 (final assessment during treatment period). Secondary efficacy endpoints included change from baseline to week 48 in growth and hepatosplenomegaly. Positive trends were observed toward increased standing height Z-score (mean [standard deviation] at baseline, −2.630 [1.17], n = 8; at week 48, −2.045 [0.27], n = 7) and growth velocity (mean [SD] Z-score at baseline, −2.59 [1.49], n = 4; at week 48, −0.39 [2.10], n = 4; p = 0.27). Hepatomegaly was resolved in 3 of 3 subjects assessed by ultrasound and in 5 of 6 subjects assessed by physical examination; splenomegaly was resolved in 1 of 3 subjects assessed by ultrasound and in 2 of 2 subjects assessed by physical examination. There were no new safety signals identified during this study. Mild-to-moderate infusion-associated reactions occurred in 4 (50%) subjects. In conclusion, long-term vestronidase alfa treatment demonstrated a rapid and sustained reduction in uGAGs, maintained growth, and improved hepatosplenomegaly in pediatric subjects with MPS VII <5 years of age.
Mediterranean Diet and its Effects on Silent Brain Infarcts in a Cohort of Patients With Atrial Fibrillation
(SAGE Publications, 2022-11-11) Escudero Martínez, Irene María; Mancha, Fernando; Vega, Ángela; Zapata, Montserrat; Ocete Pérez, Rafael F.; Álvarez, Lucía; Montaner, Joan; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Background and Aims: The benefits of Mediterranean Diet (MeDiet) in prevention of cardiovascular diseases (CVD) in general and ischemic stroke (IS) have been extensively studied and reported. We hypothesize that the consumption of nutrients typical of MeDiet would also reduce the rate of silent brain infarcts (SBI) among AF patients. Methods and Results: Patients with a history of AF who scored 0 to 1 in the CHADS2 score, ⩾50 years and with absence of neurological symptoms were selected from Seville urban area using the Andalusian electronic healthcare database. A 3T brain MRI was performed to all participants. Demographic and clinical data and food-frequency questionnaire (FFQ) were collected. Of the 443 scanned patients, 66 presented SBI. Of them 52 accepted to be scheduled for a clinical visit and were included in the diet sub study and 41 controls were matched per age and sex. There were no statistically significant differences in baseline characteristics. After logistic regression analysis, we found that a higher consumption of fiber from fruit was independently associated with a lower risk of SBI, while a higher consumption of high glycemic load (GL) foods was associated with a higher risk of SBI in a population with AF Conclusion: Our findings support that MeDiet could be suggested as a prevention strategy for SBI in patients with AF.
Papel de la proteína asociada a pancreatitis en el cribado neonatal de la fibrosis quística
(Asociación de Neumología y Cirugía Torácica del Sur (Neumosur), 2022-06-23) Delgado Pecellín, Isabel; Quintana Gallego, Esther; Mora Vallellano, Josefa; López-Campos Bodineau, José Luis; Álvarez Ríos, Ana Isabel; Moreno Valera, José; Delgado Pecellín, Carmen; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Universidad de Sevilla. Departamento de Medicina
Objetivo: El objetivo es comparar la eficacia de dos métodos de cribado de fibrosis quística (FQ) mediante la utilización de la medición del tripsinógeno inmunorreactivo (TIR) y la proteína asociada pancreatitis (PAP) en gota de sangre seca. Métodos: Estudio observacional prospectivo que evaluó a neonatos con niveles de TIR inicial (TIR1) mayor de 50ng/mL a los que se le ha realizado cuantificación de la PAP y una segunda determinación de TIR (TIR2) entre diciembre 2017 y junio 2020. Se comparó la detección de FQ entre dos protocolos de cribado TIR1/ TIR2 vs TIR1/PAP/TIR2. Resultados: Durante el período analizado se sometieron a cribado neonatal 60.399 neonatos, de los que 316 tuvieron TIR1 elevada. Se confirmaron 10 casos de FQ, con una incidencia de 1 caso por cada 6.039 neonatos cribados. El protocolo TIR1/TIR2 identificó 34 casos con una sensibilidad del 88,89%, especificidad 91,53%, valor predictivo positivo 23,53% y valor predictivo negativo de 99,65%. El protocolo TIR1/PAP/TIR2 obtuvo una sensibilidad 88,89 %, especificidad 96,42%, valor predictivo positivo 42,11% y valor predictivo negativo 99,66%. El alelo c.1521_1523delCTT se identificó en el 80% de los casos. Conclusiones: El protocolo TIR1/PAP/TIR2 aumenta la especificidad del cribado neonatal, obteniendo una disminución del 4,89% de la proporción de falsos positivos respecto al protocolo TIR1/TIR2. Este nuevo protocolo de cribado puede permitir hacer un cribado de la FQ más eficiente.
The Global Retinoblastoma Outcome Study: a prospective, cluster-based analysis of 4064 patients from 149 countries
(Elsevier, 2022-08) Fernández-Teijeiro, Ana; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Background: Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. Methods: We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. Findings: The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1–63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). Interpretation: This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.
Genotype–phenotype correlation of 17 cases of Pompe disease in Spanish patients and identification of 4 novel GAA variants
(BioMed Central, 2021-05-21) Hernández Arévalo, Paula; Santotoribio, José D.; Delarosa Rodríguez, Rocío; González-Meneses López, Antonio; García Morillo, Salvador; Jiménez Arriscado, Pilar; Guerrero Montávez, Juan Miguel; Macher, Hada C.; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI); European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
Background: Pompe disease (PD) is an autosomal recessive metabolic disorder caused by pathogenic variants in the acid α-glucosidase gene (GAA) that produces defects in the lysosomal acid α-1,4-glucosidase. We aimed to identify genetic variations and clinical features in Spanish subjects to establish genotype–phenotype correlation. Methods: A total of 2637 samples of patients who showed symptoms or susceptible signs of PD were enrolled in this observational study. Enzymatic activity was detected by fluorometric techniques and the genetic study was carried out using Next-Generation Sequencing. Results: Fourteen different variants from 17 diagnosed patients were identified, seven males and nine females with LOPD (mean age 36.07, SD 20.57, range 7–64) and a 2-day-old boy with IOPD, four genetic variants had not been described in the literature previously, including a homozygous variant. In all of them α-glucosidase activity was decreased. Muscle weakness, respiratory distress, exercise intolerance, hypotonia, dysphagia and myalgia were commonly observed in patients. Conclusions: This study report four new genetic variants that contribute to the pathogenic variants spectrum of the GAA gene. We confirm that patients in Spain have a characteristic profile of a European population, with c.-32-13T>G being the most prevalent variant. Furthermore, it was confirmed that the c.236_246delCCACACAGTGC pathogenic variant in homozygosity is associated with early disease and a worse prognosis.
Open-label phase 1/2 study of vestronidase alfa for mucopolysaccharidosis VII
(Elsevier, 2021-05-29) Jones, Simon; Coker, Mahmut; González-Meneses López, Antonio; Sniadecki, Jennifer; Mayhew, Jill; Hensman, Pauline; Jurecka, Agnieszka; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Vestronidase alfa is an enzyme replacement therapy for mucopolysaccharidosis VII (MPS VII). In this open-label, phase 1/2 study, three subjects with MPS VII received intravenous vestronidase alfa administered every other week (QOW) for 14 weeks (2 mg/kg), followed by 24-week forced-dose titration (1, 4, and 2 mg/kg QOW; 8 weeks each), 36-week continuation (2 mg/kg), and long-term extension (4 mg/kg). Vestronidase alfa was well tolerated and led to dose-responsive, sustained reductions in urinary glycosaminoglycan excretion.
Behavioral disorders and celiac disease: Coincidence or casualty?
(LIDSEN Publishing Inc., 2020-07-24) Coronel Rodríguez, Cristóbal; Rodríguez-Martínez, Alejandro; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
This paper presents the case of a child diagnosed with both celiac disease and Asperger’s syndrome. The literature does not report this association to date, and the authors believe it to be a coincidence rather than a casualty.
Impact of SARS-CoV-2 infection in patients with cystic fibrosis in Spain: Incidence and results of the national CF-COVID19-Spain survey
(Elsevier, 2020-06-20) Mondejar López, Pedro; Quintana Gallego, Esther; Girón Moreno, Rosa M.; Cortell Aznar, Isidoro; Ruiz de Valbuena-Maiz, Marta; Diab Cáceres, Layla; Andrés Martín, Anselmo; Delgado Pecellín, Isabel; Velasco González, Valle; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Background: Given the high incidence of confirmed infection by SARS-CoV-2 and mortality by COVID-19 in the Spanish population, its impact was analysed among persons with Cystic Fibrosis (CF) as a group at risk of a worse evolution. The possible causes of the incidence observed in them are explained and how CF Units have faced this health challenge is detailed. Methods: Retrospective descriptive observational study, for which a Spanish CF Patients with Confirmed COVID-19 Registry is created, requesting information on number of people affected between 8 March–16 May 2020 and their clinical-demographic characteristics from the CF Units participating in the European Cystic Fibrosis Society Patient Registry (ECFSPR). The accumulated incidence is calculated, compared with that of the general population. Additionally, a survey (CF-COVID19-Spain) is carried out on prevention of SARS-CoV-2 infection, workings of CF Units and possible reasons for the incidence observed. Results: COVID-19 was diagnosed in eight CF patients, one of whom had received a lung transplant. The accumulated incidence was 32/10000 in CF patients and 49/10000 in the general population. General death rate was 5.85/10000 while no CF patients included in the ECFSPR died. The characteristics of those affected and the results of the survey are described. Conclusions: Despite being considered a disease at high risk of severe COVID-19, the low incidence and mortality in CF patients in Spain contrasts with the figures for the general population. The possible factors that would explain such findings are discussed, with the help of the results of the CF-COVID19-Spain survey.
Monitorización domiciliaria de sodio en niños con diabetes insípida y adipsia
(Elsevier, 2020-10) Peinado Barraso, María Carmen; García García, Emilio José; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Los niños con diabetes insípida que asocian un déficit en la percepción de la sed (adipsia) pueden presentar graves oscilaciones de la natremia, que requieren frecuentes y prolongadas hospitalizaciones. Por un lado, tienen riesgo de hiponatremia por exceso hídrico por sobredosificación absoluta o relativa de desmopresina. Por otra parte, al estar abolida la sensación de sed, también tienen riesgo de hipernatremia por déficit hídrico si no se reponen bien las pérdida, (extracto)
Negative predictive value of the repeated absence of gluten immunogenic peptides in the urine of treated celiac patients in predicting mucosal healing: new proposals for follow-up in celiac diseas
(Elsevier, 2020) Ruiz Carnicer, Ángela; Garzón Benavides, Marta; Fombuena, Blanca; Segura Montero, Verónica; García-Fernández, Francisco-José; Sobrino Rodríguez, Salvador; Coronel Rodríguez, Cristóbal; Romero Gómez, Manuel; Sousa Martín, Carolina; Comino Montilla, Isabel María; Argüelles Arias, Federico; Pizarro Moreno, Ángeles; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Microbiología y Parasitología; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Junta de Andalucía; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Gobierno de España
Background: The treatment of celiac disease (CD) is a lifelong gluten-free diet (GFD). The current methods for monitoring GFD conformance, such as a dietary questionnaire or serology tests, may be inaccurate in detecting dietary transgressions, and duodenal biopsies are invasive, expensive, and not a routine monitoring technique. Objectives: Our aim was to determine the clinical usefulness of urine gluten immunogenic peptides (GIP) as a biomarker monitoring GFD adherence in celiac patients and to evaluate the concordance of the results with the degree of mucosal damage. Methods: A prospective observational study was conducted involving 22 de novo CD patients, 77 celiac patients consuming a GFD, and 13 nonceliac subjects. On 3 d of the week, urine samples were collected and the GIP concentrations were tested. Simultaneously, anti-tissue transglutaminase antibodies, questionnaire results, clinical manifestations, and histological findings were analyzed. Results: Approximately 24% (18 of 76) of the celiac patients consuming a GFD exhibited Marsh II–III mucosal damage. Among this population, 94% (17 of 18) had detectable urine GIP; however, between 60% and 80% were asymptomatic and exhibited negative serology and appropriate GFD adherence based on the questionnaire. In contrast, 97% (31 of 32) of the celiac patients without duodenal damage had no detectable GIP. These results demonstrated the high sensitivity (94%) and negative predictive value (97%) of GIP measurements in relation to duodenal biopsy findings. In the de novo CD-diagnosed cohort, 82% (18 of 22) of patients had measurable amounts of GIP in the urine. Conclusions: Determining GIP concentrations in several urine samples may be an especially convenient approach to assess recent gluten exposure in celiac patients and appears to accurately predict the absence of histological lesions. The introduction of GIP testing as an assessment technique for GFD adherence may help in ascertaining dietary compliance and to target the most suitable intervention during follow-up.
Resultados del cribado neonatal de Andalucía Occidental tras una década de experiencia
(Ministerio de Sanidad y Consumo, 2020-12-16) Delgado Pecellín, Carmen; Álvarez Ríos, Ana Isabel; Bueno Delgado, María del Amor; Jiménez Jambrina, Margarita María; Quintana Gallego, María Esther; Ruiz Salas, Pedro; Marcos Luque, Irene; Melguizo Madrid, Enrique; Delgado Pecellín, Isabel; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Fundamentos: La principal justificación del trabajo fue describir nuestra experiencia en cribado neonatal y definir la prevalencia de cada una de las enfermedades incluidas en el programa de cribado neonatal de Andalucía, entre las que se encuentran el hipotiroidismo congénito, cribado ampliado expandido (aminoacidopatías, defectos de la beta-oxidación mitocondrial y acidurias orgánicas), fibrosis quística y enfermedad de células falciformes. Métodos: El estudio se realizó en la Unidad del Laboratorio de Metabolopatías del Hospital Universitario Virgen del Rocío de Sevilla con muestras de recién nacidos de Andalucía Occidental (Cádiz, Córdoba, Huelva y Sevilla) y la ciudad autónoma de Ceuta. Para descartar hipotiroidismo congénito y cribado ampliado expandido se estudiaron un total de 435.141 recién nacidos, con fecha de inicio el 1 de abril de 2009. El cribado de fibrosis quística comenzó el 1 de mayo de 2011, siendo estudiados un total de 378.306 recién nacidos. Por último, el 26 de noviembre de 2018 se incorporó el cribado de anemia de células falciformes, que comprendió un total de 55.576 recién nacidos. La fecha fin de estudio fue el 31 de diciembre de 2019 para todas las patologías descritas anteriormente. El análisis estadístico se realizó usando el software IBM SPSS (versión 22, SPSS INC., EEUU). Resultados: El estudio reveló una prevalencia de 1:1.565 recién nacidos para hipotiroidismo congénito, 1:1.532 para cribado ampliado expandido, 1:6.878 para fibrosis quística y 1:11.115 recién nacidos para enfermedad de células falciformes. Conclusiones: El programa de cribado neonatal permite que se beneficien gran número de recién nacidos en la detección precoz de determinadas enfermedades congénitas graves y, con ello, mejora la morbimortalidad de aquellos que las padecen.
Risk and Response Adapted Treatment Guidelines for Managing First Relapsed and Refractory Classical Hodgkin Lymphoma in Children and Young People. Recommendations from the EuroNet Pediatric Hodgkin Lymphoma Group
(Wiley, 2020-01-10) Daw, Stephen; Hasenclever, Dirk; Mascarin, Maurizio; Fernández-Teijeiro, Ana; Balwierz, Walentyna; Beishuizen, Auke; Leblanc, Thierry; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
The objective of this guideline is to aid clinicians in making individual salvage treatment plans for pediatric and adolescent patients with first relapse or refractory (R/R) classical Hodgkin lymphoma (cHL). While salvage with standard dose chemotherapy followed by high dose chemotherapy and autologous stem cell transplant is often considered the standard of care in adult practice, pediatric practice adopts a more individualized risk stratified and response adapted approach to salvage treatment with greater use of non-transplant salvage. Here, we present on behalf of the EuroNet Pediatric Hodgkin Lymphoma group, evidence and consensus-based guidelines for standardized diagnostic, prognostic and response procedures to allocate children and adolescents with R/R cHL to stratified salvage treatments.
Alergia a las proteínas de leche de vaca no mediada por IgE: documento de consenso de la Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP), la Asociación Española de Pediatría de Atención Primaria (AEPAP), la Sociedad Española de Pediatría Extrahospitalaria y Atención Primaria (SEPEAP) y la Sociedad Española de Inmunología Clínica, Alergología y Asma Pediátrica (SEICAP)
(Elsevier, 2019-01-19) Espín Jaime, Beatriz; Díaz Martín, Juan J.; Blesa Baviera, Luis Carlos; Claver Monzón, Ángela; Hernández Hernández, Anselmo; García Burriel, José Ignacio; García Mérida, María José; Pinto Fernández, Celia; Coronel Rodríguez, Cristóbal; Román Riechmann, Enriqueta; Ribes Koninckx, Carmen; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
La alergia a las proteínas de leche de vaca no mediada por IgE es una patología frecuente, en cuyo manejo están implicados profesionales de diferentes áreas existiendo a día de hoy una gran variabilidad en la forma de abordar su diagnóstico, tratamiento, seguimiento y prevención. Con el objetivo de unificar pautas de actuación se ha elaborado un documento de consenso entre cuatro de las sociedades científicas implicadas en el abordaje de niños con dicha patología.
ECLIM-SEHOP, a new platform to set up and develop international academic clinical trials for childhood cancer and blood disorders in Spain
(Springer, 2019-10-09) Bautista, F.; Cañete, A.; Ramírez Villar, G.L.; Fernández, J.M.; Fuster, J.L.; Diaz de Heredia, C.; Márquez Vega, Catalina; Fernández Teijeiro, A.; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Asociación Pablo Ugarte; Federación Española de Padres de Niños con Cáncer; Fundación Inocente Inocente; Fundación MAR; Asociación Española Contra el Cáncer (AECC)
Introduction: Cancer and blood disorders in children are rare. The progressive improvement in survival over the last decades largely relies on the development of international academic clinical trials that gather the sufficient number of patients globally to elaborate solid conclusions and drive changes in clinical practice. The participation of Spain into large international academic trials has traditionally lagged behind of other European countries, mainly due to the burden of administrative tasks to open new studies, lack of financial support and limited research infrastructure in our hospitals. Methods: The objective of ECLIM-SEHOP platform (Ensayos Clínicos Internacionales Multicéntricos-SEHOP) is to overcome these difficulties and position Spain among the European countries leading the advances in cancer and blood disorders, facilitate the access of our patients to novel diagnostic and therapeutic approaches and, most importantly, continue to improve survival and reducing long-term sequelae. ECLIM-SEHOP provides to the Spanish clinical investigators with the necessary infrastructural support to open and implement academic clinical trials and registries. Results: In less than 3 years from its inception, the platform has provided support to 20 clinical trials and 8 observational studies, including 8 trials and 4 observational studies where the platform performs all trial-related tasks (integral support: trial setup, monitoring, etc.) with more than 150 patients recruited since 2017 to these studies. In this manuscript, we provide baseline metrics for academic clinical trial performance that permit future comparisons. Conclusions: ECLIM-SEHOP facilitates Spanish children and adolescents diagnosed with cancer and blood disorders to access state-of-the-art diagnostic and therapeutic strategies.

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